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New immunotherapy for treatment of metastatic melanoma doubles the progression-free survival!

 Last Update: 2021-06-03
 Source: Internet
 Author: User

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Recently, the combination therapy of LAG-3 antibody Relatlimab and "O drug" nivolumab has performed amazingly in clinical trials for the treatment of patients with melanoma.

▌Fatal metastatic melanoma

Melanoma is a type of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin.

When cancer cells spread outside the skin and affect other organs, it is called metastatic melanoma, which is also the most deadly form of the disease.

In the past 30 years, the incidence of melanoma has been steadily increasing.
According to estimates by the World Health Organization, by 2035, the global incidence of melanoma will reach 424,000 cases, with nearly 100,000 deaths.

Early melanoma can be cured.
Once it spreads to the local lymph nodes, the patient's survival rate will be greatly reduced, and better treatments are urgently needed.

▌New immunosuppressant target: LAG-3

Lymphocyte activation gene 3 (LAG-3) is a cell surface molecule expressed on effector T cells and regulatory T cells (Tregs).
Its function is to control T cell response, activation and growth.

Preclinical studies have shown that inhibiting LAG-3 can restore the effector function of exhausted T cells and promote their anti-tumor response.
Early studies have shown that targeting LAG-3 combined with other potentially complementary immune checkpoints may be more effective in enhancing anti-tumor immune activity.

Relatlimab is the third unique checkpoint inhibitor besides anti-PD-1 and anti-CTLA-4.
By blocking the signal pathway mediated by LAG-3, combined with PD-1 inhibitors, it can produce synergistic pain, activate T cells, trigger an immune response, and promote tumor cell death.

Previously, nivolumab and "Y drug" ipilimumab were jointly approved for the treatment of melanoma, and it has been approved in more than 50 countries/regions, including the United States and the European Union.

▌Progress-free survival is doubled! Combination therapy is effective

RELATIVITY-047 (CA224-047) is a global, randomized, double-blind Phase 2/3 study that evaluated the fixed-dose combination therapy of nivolumab + Relatlimab and single-agent nivolumab in untreated Efficacy and safety in patients with metastatic or unresectable melanoma.

A total of 714 patients were enrolled in the trial, and they were randomly allocated at a ratio of 1:1 until the disease recurred or unacceptable toxicity occurred.
The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival (OS) and objective response rate (ORR).

The results show that:

Compared with the nivolumab monotherapy group, the median PFS of patients in the fixed-dose combination therapy group was significantly prolonged, which was 10.
12 months VS 4.
63 months, which had a statistically significant clinical benefit.

The secondary endpoint OS and ORR data will be announced at the 2021 American Society of Clinical Oncology (ASCO) annual meeting in June.

At the same time, the safety of the fixed-dose combination is controllable and consistent with previously reported single-dose safety.

Over the years, immune checkpoint inhibitors have made great progress in treatment and have brought long-term survival benefits.
However, there are still patients with metastatic melanoma who can benefit from another innovative approach.

In addition, Fianlimab, another LAG-3 inhibitor, combined with the PD-1 inhibitor Libtayo (Cemiplimab), also showed strong efficacy in patients with advanced melanoma.
The objective response rate (ORR) of the dual immune combination therapy group reached 64%, and the safety was good.

LAG-3 not only represents a new immunotherapy target, but can also be combined with other PD-1 inhibitors to improve anti-tumor activity and bring new hope for potential treatment for patients with advanced cancer.

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